Breast cancer and lung cancer, both being solid tumors, have been considered as major causes of cancer deaths regardless of multimodality therapies therefor. Radiation therapy is a general therapeutic method performed on a solid tumor patient. Solid tumor patients account for about 40% to 60% of cancer patients receiving radiation therapy. However, solid tumors have been known to show radioresistance which reduces the killing of cancer cells by radiation therapy. Accordingly, for effective cancer treatment, there is a need for the development of a radiosensitizer that can enhance cancer cell killing by irradiation.
An miRNA (microRNA) is a very small single stranded ribonucleic acid (RNA) consisting of about 21 to 23 nucleotides, found in cells. About a few hundred miRNAs are known to be present in humans, and to be involved in biological phenomena such as development, growth, aging and death via regulation of gene expression. Due to the distinctive expression patterns of miRNA in normal tissues and cancer tissues, the utility of miRNA as a predictive biomarker has been noted. In particular, miR-21 has been known to mediate the pathophysiological mechanism of tumor development by playing a critical role in proliferation, invasion and metastasis of a tumor by targeting a tumor suppressor gene.
Ionizing radiation (IR) eventually leads to deoxribonucleic acid (DNA) damage in cells, thereby causing cell death. A double strand break (DSB) due to IR induces DNA damage response (DDR) signal transduction, which is known to determine cell cycle arrest for DNA repair or apoptosis due to excessive DNA damage. miRNAs which target major genes involved in the DDR signal transduction have been already reported, and thus miRNAs' new roles in the radiation induced DDR signal transduction are of great concern. With new human miRNAs being continuously discovered, there has been an increasing need for the development of a therapeutic agent that is capable of enhancing radiation sensitivity while minimizing any adverse effect, thereby providing effective therapy to be combined with radiation therapy.
Accordingly, the inventors of the present invention have focused their research on miRNA which can be used as a radiosensitizer in combination with radiation therapy by acting on major genes involved in the DDR signal transduction, and succeeded in developing miRNA capable of increasing radiation sensitivity of radioresistant cancer cells.
These and/or other aspects will become apparent and more readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings.